Generation of induced pluripotent stem cells and mesenchymal stromal cells.

Abstract

Mesenchymal stromal cells (MSCs) are a population of mesoderm-derived cells that possess the ability to differentiate into bone, cartilage, and adipose tissue. They are important to understanding the developmental process of musculoskeletal tissue, and can be utilized for novel human cell therapies. Previous studies by our group and others have demonstrated development of MSCs from human embryonic stem cells (hESCs). Now, we have identified a population of potential mesenchymal precursor cells from adult bone marrow derived iPSC lines using CD73 as a selection marker. Sorting and culture of the hESC/iPSC-derived CD73-positive cells lead to development of MSCs capable of making bone, cartilage, and adipocytes. However the variations in differentiation methods have been found to strongly influence their mesenchyme induction and their ability to make bone, cartilage and adipose tissue. We compare the spin EB (embryoid body) versus stromal co-culture techniques to arrive at a MSC population in our studies. Additionally, these studies examined novel ways to derive iPSCs that could be used for derivation of MSCs and other cell populations. Induced pluripotent stem cells have previously been generated from human dermal fibroblast cells. However, the requirement for skin biopsies and the need to expand fibroblast cells for several passages in vitro make it a cumbersome source for generating patient-specific stem cells. Reprogramming from human blood cells represents a consistent method of establishing patient-specific iPSCs.